The long-term objectives of the present proposal is to study the physiology and plasticity of excitatory synapses in the rat visual cortex. It is proposed here to study glutamate receptor heterogeneity and processes regulating miniature EPSCs using new information and techniques resulting from research done under the current grant. Specifically, the aims of this proposal are: l. Characterization of the developmental regulation of NMDA receptor- channels in layers II-IV of rat visual cortex. 2. Regulation of miniature EPSC in layers II-IV of the rat visual cortex by calcium, protein phosphorylation and activation of metabotropic receptors. 3. Comparison among glutamate receptors in pyramidal and non-pyramidal neurons in layers II-IV of the rat visual cortex. Understanding how excitatory synapses operate in the visual cortex and how they are regulated is critical for understanding cortical function. Yet, the diversity of cortical neurons and synapses and their complex anatomical connections represents a major challenge. Using mEPSCs avoids problems associated with polysynaptic circuits and could distinguish between pre and post synaptic mechanisms. The experiments proposed here would examine the effects of manipulations, mimicking endogenous signals, on the properties of mEPSCs. Results obtained, under the current grant, using patch-clamp recording showed that NMDA receptors undergo developmental changes and that AMPA/Kainate receptors expressed in pyramidal neurons are different than those expressed in aspiny interneurons. It is proposed to characterize glutamate receptor properties (e.g., single-channel conductance; Mg2+ sensitivity, kinetics) during development in morphologically identified neurons.